Increased Susceptibility to RSV Infection by Exposure to Inhaled Diesel Engine Emissions

Abstract

Although epidemiologic data strongly suggest a role for inhaled environmental pollutants in modulating the susceptibility to respiratory infection in humans, the underlying cellular and molecular mechanisms have not been well studied in experimental systems. The current study assessed the impact of inhaled diesel engine emissions (DEE) on the host response in vivo to a common pediatric respiratory pathogen, respiratory syncytial virus (RSV). Using a relatively resistant mouse model of RSV infection, prior exposure to either 30 microg/m3 particulate matter (PM) or 1,000 microg/m3 PM of inhaled DEE (6 h/d for seven consecutive days) increased lung inflammation to RSV infection as compared with air-exposed RSV-infected C57Bl/6 mice. Inflammatory cells in bronchoalveolar lavage fluid were increased in a dose-dependent manner with regard to the level of DEE exposure, concomitant with increased levels of inflammatory mediators. Lung histology analysis indicated pronounced peribronchial and peribronchiolar inflammation concordant with the level of DEE exposure during infection. Mucous cell metaplasia was markedly increased in the airway epithelium of DEE-exposed mice following RSV infection. Interestingly, both airway and alveolar host defense and immunomodulatory proteins were attenuated during RSV infection by prior DEE exposure. DEE-induced changes in inflammatory and lung epithelial responses to infection were associated with increased RSV gene expression in the lungs following DEE exposure. These findings are consistent with the concept that DEE exposure modulates the lung host defense to respiratory viral infections and may alter the susceptibility to respiratory infections leading to increased lung disease.

Household Conditions, Eczema Symptoms and Rhinitis Symptoms: Relationship with Wheeze and Severe Wheeze in Children Living in the Polokwane Area, South Africa

“…Studies indicate that virus-induced inflammation in the upper and lower respiratory tract may be exacerbated by concurrent exposure to low levels of diesel exhaust particulate matter, nitrogen dioxide and ozone commonly encountered in indoor and outdoor environments [51,52].…”

IL-12p40 and IL-18 Modulate Inflammatory and Immune Responses to Respiratory Syncytial Virus Infection

“…A syringe containing inoculant was expelled into the trachea followed by multiple injections of air to facilitate dispersion of inoculant into the lung periphery. Mice usually recovered within 5 min and resumed normal eating and grooming activities (26,27). Sterile medium (100 l/mouse) was used as control.…”

“…instillations of 0.6 ml of PBS into the right lung using a fine catheter tied to the right main bronchus, and the samples were pooled for each animal. The BALF was processed, and the total and differential cells were counted as described elsewhere (26,27). The remaining lung tissues were then used for histopathological and molecular studies as described below.…”

Acute diesel exhaust particle exposure increases viral titre and inflammation associated with existing influenza infection, but does not exacerbate deficits in lung function

“…Accordingly, experimental studies investigating the impacts of DEP on responses to respiratory viral infection are sparse and are typically in vitro in nature, 12 , 13 or involve animal models of long‐term exposure to DE 14 , 15 , 16 . Furthermore, such studies usually entail exposing test animals to DE prior to infection to test the effects of exposure on susceptibility to infection 14 , 15 , 16 .…”

“…Furthermore, such studies usually entail exposing test animals to DE prior to infection to test the effects of exposure on susceptibility to infection 14 , 15 , 16 . Such studies have shown that exposure to DE results in increased susceptibility to respiratory viral infection, 14 , 15 , 16 higher viral replication, 15 increased pulmonary inflammation, 14 , 16 lower interferon levels 15 , 17 and up‐regulation of Toll‐like receptor 3 (TLR3) receptor expression and signalling 16 in mice.…”